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1.
J Anim Breed Genet ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291375

RESUMEN

This study aimed to estimate variance components (VCs) for growth and reproductive traits in Nellore cattle using two relationship matrices (pedigree relationship A matrix and pedigree plus genomic relationship H matrix), and records collected before and after genomic selection (GS) implementation. The study also evaluated how genomic breeding values (GEBV) are affected by variance components and discarding old records. The analysed traits were weight at 120 days (W120), weight and scrotal circumference at 450 days (W450 and SC450, respectively). Three datasets were used to estimate VCs, including all phenotypic information (All) or records for animals born before or after GS implementation (Before or After datasets, respectively). Both relationship matrices were considered for VC estimation, the A matrix was used in all three datasets and VC from each combination were named as A_Before, A_After, and A_All). The H was used in two datasets: H_All and H_After. Different VCs were used for GEBV prediction through ssGBLUP. This step used two possible Datasets, using all available phenotypic data (Dataset 1) or just records collected since GS implementation (Dataset 2). Validation was conducted using accuracy, bias and dispersion according to the LR method and prediction accuracy from corrected phenotypes. The heritability of all traits increased from A_Before to A_After, while estimates for A_All were intermediary. In the previous order, the estimates were 0.16, 0.17, and 0.15 for W120; 0.31, 0.39, and 0.35 for W450; 0.35, 0.47, and 0.41 for SC. For W450 and SC, using the H matrix reduced the heritability (0.33 and 0.32 for W450; 0.41 and 0.38 for SC for H_After and H_All, respectively). For W120, Dataset1 and VCs from A_After showed the highest accuracy for direct and maternal GEBV (0.953 and 0.868). For W450, Dataset 1 and VC from H_After allowed the highest accuracy (0.854) but use Dataset 2 and same VC source yield similar value (0.846). For SC, Dataset 2 with VC from H_After showed the highest accuracy (0.925). To use Dataset 2 does not cause important changes in bias or dispersion with respect to Dataset 1. The VC and genetic parameters changed for W120, W450, and SC450, using records before or after the GS implementation. For W450 and SC450, genetic variance and heritability estimates increased with the use of GS. For W120, genomic predictions were more accurate using A for VC estimation. Accuracy gains were observed for W450 and SC450 using H in VC estimation and/or discarding records before GS. It is possible to discard phenotypic records before GS implementation without generating bias or dispersion in the GEBV of young candidates.

2.
Trop Anim Health Prod ; 56(8): 258, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39289187

RESUMEN

Milk production in tropical regions plays a crucial role both economically and socially. Typically, animals are utilized for dual purposes and are genetically obtained by an intense crossbreeding between Zebu and/or locally adapted breeds, alongside specialized breeds for dairy production. However, uncontrolled mating and crossbreeding may affect the establishment of an effective animal breeding program. The objective of this study was to evaluate Genomic diversity of highly crossbred cattle population in a Low and Middle Tropical environment. All sampled animals were genotyped using the Genessek GGP Bovine 100 chip (n = 859) and public genomic information from eight breeds were employed as reference. The genetic structure of the population was estimated using a Principal Component, Bayesian clustering and a linkage disequilibrium analysis. PCA results revealed that PC1 explained 44.39% of the variation, associated with the indicus/taurus differentiation, and PC2 explained 14.6% of the variation, attributed to the differentiation of Creole and European components. This analysis underscored a low population structure, attributed to the absence of genealogical tracking and the implementation of non-directed crossbreeding. The clustering shows an average contribution of Zebu, Creole, and European Taurine components in the population was 53.26%, 27.60%, and 19.13%, respectively. While an average LD of 0.096 was obtained for a maximum distance of 400 kb. The LD value was low in this population, probably due to the almost no selection applied and the recombination events that occurred during its development. These findings underscore the value of crossbreeding in tropical dairy production but emphasize the importance of directing the mattings.


Asunto(s)
Variación Genética , Hibridación Genética , Clima Tropical , Animales , Bovinos/genética , Bovinos/fisiología , Desequilibrio de Ligamiento , Teorema de Bayes , Genotipo , Cruzamiento , Femenino , Análisis de Componente Principal , Brasil , Masculino
3.
J Mol Diagn ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276924

RESUMEN

Alpha-1 antitrypsin (AAT) is an acute-phase reactant with immunomodulatory properties that mainly inhibits neutrophil elastase. Low serum levels cause AAT deficiency (AATD), an underdiagnosed condition that predisposes to pulmonary and hepatic diseases. The SERPINA1 gene, which encodes AAT, contains more than 500 variants. PI*Z and PI*S alleles are the most diagnosed causes of AATD, but the role of the SERPINA1 haplotypes in AAT function remains unknown. SERPINA1 gene was PCR amplified from 94 asthma patients, using primers with tails for indexing. Sequencing libraries were loaded into a MinION-Mk1C, and MinKNOW was used for basecalling and demultiplexing. Nanofilt and Minimap2 were used for filtering and mapping/alignment. Variant calling/phasing were performed with PEPPER-Margin-DeepVariant. SERPINA1 gene was 100% covered for all samples, with a minimum sequencing depth of 500X. 75 single nucleotide variants and 4 indels were detected, with 45 and 2 of them highly polymorphic (MAF>0.1), respectively. Nine of the SNVs showed differences in allele frequencies when compared with the overall Spanish population. More than 90% of heterozygous SNVs were phased, yielding 91 and 58 different haplotypes for each SERPINA1 amplified region. Haplotype-based Linkage Disequilibrium (LD) analysis suggests that a recombination hotspot could generate variation in the SERPINA1 gene. The proposed workflow enables haplotype-aware genotyping of the SERPINA1 gene by nanopore sequencing, which will allow the development of novel AATD diagnostic strategies.

4.
J Texture Stud ; 55(5): e12865, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39245871

RESUMEN

The objective of this study was to study the impact of pressing time on the microstructure of goat cheese and its relationship with sensory attributes. The microstructure of the artisanal cheeses was performed by scanning electron microscopy and image analysis. The validation of the microstructural complexity was carried out experimentally with sensory attributes. The pressing time influenced the microstructural parameters Feretmax, Geodiam, and τ and the cheese type influenced the parameters Feretmax, Geodiam, and Geoelong. The correlation values between microstructural complexity and sensory attributes were 0.85 and 0.84 for fresh cheeses and matured cheeses, respectively. The pressure times of 12 and 18 h resulted in cheese microstructures with the highest complexity in terms of Feretmax, Geodiam, Geoelong, and τ parameters. The obtained results are supported by the correlation values between microstructural complexity and sensory attributes.


Asunto(s)
Queso , Manipulación de Alimentos , Cabras , Microscopía Electrónica de Rastreo , Gusto , Queso/análisis , Animales , Humanos , Factores de Tiempo , Presión
5.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1569238

RESUMEN

Objective: To evaluate the effect of melatonin as a protective treatment for the tongue in irradiated rats. Materials and Methods: Male Sprague Dawley rats were subjected to a single session of 50 Gy radiation and treated with melatonin 30 minutes before and after the radiotherapy session. A clinical evaluation was carried out a week and a half, third- and sixth-week post-treatment; finally, a tongue biopsy was taken for a histopathological study in the third and sixth weeks after radiation. Results: Clinical evaluation shows a clear trend, that preventive administration of melatonin could facilitate the recovery of mucosal tissue after radiation. Additionally, cellular infiltrate was 40% fewer in the melatonin-treated group compared to the control, as well as the number of the congested vessel were fewer. Conclusion: These findings showed for the first time the preventive role of melatonin in the tongue mucosa reducing the changes associated with mucositis, inflammatory infiltrate, and congestive blood vessels.

6.
Crit Care Sci ; 36: e20240044en, 2024.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-39140527

RESUMEN

OBJECTIVE: Patients with acute respiratory failure often require mechanical ventilation to reduce the work of breathing and improve gas exchange; however, this may exacerbate lung injury. Protective ventilation strategies, characterized by low tidal volumes (≤ 8mL/kg of predicted body weight) and limited plateau pressure below 30cmH2O, have shown improved outcomes in patients with acute respiratory distress syndrome. However, in the transition to spontaneous ventilation, it can be challenging to maintain tidal volume within protective levels, and it is unclear whether low tidal volumes during spontaneous ventilation impact patient outcomes. We developed a study protocol to estimate the prevalence of low tidal volume ventilation in the first 24 hours of spontaneous ventilation in patients with hypoxemic acute respiratory failure and its association with ventilator-free days and survival. METHODS: We designed a multicenter, multinational, cohort study with a 28-day follow-up that will include patients with acute respiratory failure, defined as a partial oxygen pressure/fraction of inspired oxygen ratio < 300mmHg, in transition to spontaneous ventilation in intensive care units in Latin America. RESULTS: We plan to include 422 patients in ten countries. The primary outcomes are the prevalence of low tidal volume in the first 24 hours of spontaneous ventilation and ventilator-free days on day 28. The secondary outcomes are intensive care unit and hospital mortality, incidence of asynchrony and return to controlled ventilation and sedation. CONCLUSION: In this study, we will assess the prevalence of low tidal volume during spontaneous ventilation and its association with clinical outcomes, which can inform clinical practice and future clinical trials.


Asunto(s)
Unidades de Cuidados Intensivos , Síndrome de Dificultad Respiratoria , Volumen de Ventilación Pulmonar , Humanos , América Latina/epidemiología , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/epidemiología , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/mortalidad , Respiración Artificial , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/epidemiología
7.
Int J Mol Sci ; 25(15)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39125649

RESUMEN

lncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Terapia Neoadyuvante , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Resistencia a Antineoplásicos/genética , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Perfilación de la Expresión Génica , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Transcriptoma
8.
J Dent ; 150: 105327, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39197532

RESUMEN

OBJECTIVE: To evaluate the perceptibility and acceptability CIEDE2000 (KL:KC:KH) thresholds for lightness, chroma and hue differences in dentistry. METHOD: A Python-based program was developed to conduct a psychophysical experiment based on visual assessments of computer-simulated images of human teeth. The experiment was performed on a calibrated display. A 40-observer panel: dentists and laypersons (male and female; n=10), evalu- ated three subsets of simulated human teeth: the lightness subset (%∆L00 ≥ 98 %), the chroma subset (%∆C00 ≥ 98 %) and the hue subset (%∆H00 ≥ 98 %), using ∆E00 ≥ 5 units. A Takagi-Sugeno-Kang Fuzzy Approximation model was used as fitting procedure, and 50:50 % lightness, chroma and hue CIEDE2000 (1:1:1) and CIEDE2000 (2:1:1) perceptibility (PT00) and accept- ability (AT00) thresholds were calculated. Data was statistically analyzed using t-test (p < 0.05). RESULTS: The 50:50 % PT00 for KL=1 were ∆L00=1.04, ∆C00=1.58 and ∆E00=1.01; and for KL=2 were ∆L00=0.51, ∆C00=1.58 and ∆E00=0.71. The 50:50 % AT00 for KL=1 were ∆L00=2.82, ∆C00=3.04 and ∆E00=2.66; and for KL=2 were ∆L00=1.40, ∆C00=3.04 and ∆E00=1.78. PT00 and AT00 ∆H00 may be considered no computable. A significant difference was found between CIEDE2000(1:1:1) and CIEDE2000(2:1:1), between lightness and chroma metrics, and between observer groups. No differences for lightness and chroma PT00 were found between male and female groups. CONCLUSIONS: It is important to use PT00 and AT00 for lightness, chroma and hue specific to evaluate perceptual sensitivity for color changes in the tooth color space. AT00 for lightness and chroma are influenced by the observer's experience and gender. Males and laypersons show more tolerance for changes in chroma (∆C00) and in lightness (∆L00). SIGNIFICANCE: Hue and chroma mismatch are more difficult to be accepted in dental color space.

9.
Dent Mater ; 40(10): 1677-1684, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39097503

RESUMEN

OBJECTIVE: To assess the prediction accuracy of recent optical and numerical models for the spectral reflectance and color of monolithic samples of dental materials with different thicknesses. METHODS: Samples of dental resin composites of Aura Easy Flow (Ae1, Ae3 and Ae4 shades) and Estelite Universal Flow Super Low (A1, A2, A3, A3.5, A4 and A5 shades) with thicknesses between 0.3 and 1.8 mm, as well as Estelite Universal Flow Medium (A2, A3, OA2 and OA3 shades) with thicknesses between 0.4 and 2.0 mm, were used. Spectral reflectance and transmittance factors of all samples were measured using a X-Rite Color i7 spectrophotometer. Four analytical optical models (2 two-flux models and 2 four-flux models) and two numerical models (PCA-based and L*a*b*-based) were implemented to predict spectral reflectance of all samples and then convert them into CIE-L*a*b* color coordinates (D65 illuminant, 2°Observer). The CIEDE2000 total color difference formula (ΔE00) between predicted and measured colors, and the corresponding 50:50% acceptability and perceptibility thresholds (AT00 and PT00) were used for performance assessment. RESULTS: The best performing optical model was the four-flux model RTE-4F-RT, with an average ΔE00 = 0.72 over all samples, 94.87% of the differences below AT00 and 65.38% below PT00. The best performing numerical model was L*a*b*-PCHIP (interpolation mode), with an average ΔE00 = 0.48, and 100% and 79.69% of the differences below AT00 and PT00, respectively. SIGNIFICANCE: Both optical and numerical models offer comparable color prediction accuracy, offering flexibility in model choice. These results help guide decision-making on prediction methods by clarifying their strengths and limitations.


Asunto(s)
Color , Resinas Compuestas , Ensayo de Materiales , Espectrofotometría , Resinas Compuestas/química , Materiales Dentales/química
10.
Sci Rep ; 14(1): 19669, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39181908

RESUMEN

In this study, thermoplastic starch (TPS) biofilms were developed using starch isolated from the seeds of Melicoccus bijugatus (huaya) and reinforced with bentonite clays at concentrations of 1%, 3%, and 5% by weight. Novelty of this research lies in utilizing a non-conventional starch source and enhancing properties of TPS through clay reinforcement. FTIR analysis verified bentonite's nature of clays, while SEM analysis provided insights into morphology and agglomeration behavior. Key findings include a notable increase in biofilm thickness and elastic modulus with higher clay content. Specifically, tensile strength of biofilms improved from 2.5 MPa for pure TPS to 5.0 MPa with 5% clay reinforcement. The elastic modulus increased from 25 MPa (TPS) to 60 MPa (5% clay). Thermal stability also showed enhancement, with initial degradation temperature increasing from 110 °C for pure TPS to 130 °C for TPS with 5% clay. Water vapor permeability (WVP) tests demonstrated a decrease in WVP values from 4.11 × 10-10 g m-1 s-1 Pa-1 for pure TPS to 2.09 × 10-10 g m-1 s-1·Pa-1 for TPS with 5% clay, indicating a significant barrier effect due to clay dispersion. These results suggest that biofilms based on huaya starch and reinforced with bentonite clay have considerable potential for sustainable food packaging applications, offering enhanced mechanical and barrier properties.

11.
Discov Oncol ; 15(1): 378, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196408

RESUMEN

BACKGROUND: Health disparities have been highlighted among patient with prostate adenocarcinoma (PRAD) due to ethnicity. Mexican men present a more aggressive disease than other patients resulting in less favorable treatment outcome. We aimed to identify the mutational landscape which could help to reduce the health disparities among minority groups and generate the first genomics exploratory study of PRAD in Mexican patients. METHODS: Paraffin-embedded formalin-fixed tumoral tissue from 20 Mexican patients with early-stage PRAD treated at The Instituto Nacional de Cancerología, Mexico City from 2017 to 2019 were analyzed. Tumoral DNA was prepared for whole exome sequencing, the resulting files were mapped against h19 using BWA-MEM. Strelka2 and Lancet packages were used to identify single nucleotide variants (SNV) and insertions or deletions. FACETS was used to determine somatic copy number alterations (SCNA). Cancer Genome Interpreter web interface was used to determine the clinical relevance of variants. RESULTS: Patients were in an early clinical stage and had a mean age of 59.55 years (standard deviation [SD]: 7.1 years) with 90% of them having a Gleason Score of 7. Follow-up time was 48.50 months (SD: 32.77) with recurrences and progression in 30% and 15% of the patients, respectively. NUP98 (20%), CSMD3 (15%) and FAT1 (15%) were the genes most frequently affected by SNV; ARAF (75%) and ZNF419 (70%) were the most frequently affected by losses and gains SNCA's. One quarter of the patients had mutations useful as biomarkers for the use of PARP inhibitors, they comprise mutations in BRCA, RAD54L and ATM. SBS05, DBS03 and ID08 were the most common mutational signatures present in this cohort. No associations with recurrence or progression were identified. CONCLUSIONS: This pilot study reveals the mutational landscape of early-stage prostate adenocarcinoma in Mexican men, providing a first approach to understand the mutational patterns and actionable mutations in early prostate cancer can inform personalized treatment approaches and reduce the underrepresentation in genomic cancer studies.

12.
Respir Med Case Rep ; 50: 102064, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962486

RESUMEN

A 48-year-old woman presented to the emergency department with a one-week history of progressive dyspnea. During her hospitalization, the diagnosis of diffuse alveolar hemorrhage was made. She subsequently developed respiratory failure and acute right ventricular failure. Despite medical treatment, she continued to experience distributive shock due to a generalized inflammatory response. Circulatory support with ECMO was needed. We opted for triple cannulation to manage the multiorgan failure as a bridge to recovery. We describe our experience with an uncommon cannulation technique: veno-pulmonary-arterial cannulation, which enabled us to address cardiogenic shock, refractory hypoxemia, and distributive shock, leading to the successful recovery of the patient.

13.
ChemMedChem ; : e202400144, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049537

RESUMEN

This study explores various aspects of Metal-Organic Frameworks (MOFs), focusing on synthesis techniques to adjust pore size and key ligands and metals for crafting carrier MOFs. It investigates MOF-drug interactions, including hydrogen bonding, van der Waals, and electrostatic interactions, along with kinetic studies. The multifaceted applications of MOFs in drug delivery systems are elucidated. The morphology and structure of MOFs are intricately linked to synthesis methodology, impacting attributes like crystallinity, porosity, and surface area. Hydrothermal synthesis yields MOFs with high crystallinity, suitable for catalytic applications, while solvothermal synthesis generates MOFs with increased porosity, ideal for gas and liquid adsorption. Understanding MOF-drug interactions is crucial for optimizing drug delivery, affecting charge capacity, stability, and therapeutic efficacy. Kinetic studies determine drug release rates and uniformity, vital for controlled drug delivery. Overall, comprehending drug-MOF interactions and kinetics is essential for developing effective and controllable drug delivery systems.

14.
Arch Med Sci ; 20(3): 1016-1021, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050166

RESUMEN

Introduction: Atrophic gastritis and intestinal metaplasia are precursor lesions of gastric cancer. The aim of this study was to determine the usefulness of the biomarkers pepsinogen I(PgI), pepsinogen II (PgII), gastrin-17, and H. pylori antibodies in the identification of precursor lesions. Methods: We studied 129 patients with gastric symptoms. The biomarker status was determined using GastroPanel by means of the ELISA-technique. Results: Biomarkers detected atrophy in 14% of the subjects, and 49.6% had positive antibodies for H. pylori. A PgI/PgII ratio < 3 was an important risk biomarker for precursor lesions in our population (OR = 9.171, 95% CI: 1.723-48.799, p = 0.009); however, biomarkers showed low accuracy with histopathological study. Conclusions: In the Western Mexican population, precursor lesions (AG, IM) are common in adults (45%) with dyspepsia but infrequent in children (8%). H. pylori infection was detected in 41.3% of adults and 16.0% of children. Of the studied biomarkers, a PgI/PgII ratio < 3 was an important risk factor for precursor lesions such as AG or IM in our population, with an OR of 9.171 (95% CI: 1.723-48.799, p = 0.009).

15.
Clin Chest Med ; 45(3): 599-610, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39069324

RESUMEN

Asthma is a common complex airway disease whose prediction of disease risk and most severe outcomes is crucial in clinical practice for adequate clinical management. This review discusses the latest findings in asthma genomics and current obstacles faced in moving forward to translational medicine. While genome-wide association studies have provided valuable insights into the genetic basis of asthma, there are challenges that must be addressed to improve disease prediction, such as the need for diverse representation, the functional characterization of genetic variants identified, variant selection for genetic testing, and refining prediction models using polygenic risk scores.


Asunto(s)
Asma , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genómica , Humanos , Asma/genética , Asma/diagnóstico , Medición de Riesgo , Pruebas Genéticas
16.
Medicine (Baltimore) ; 103(30): e38776, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39058801

RESUMEN

Several risk factors were associated with mortality in patients with coronavirus disease 2019 (COVID-19) infection in intensive care units (ICU). We assessed the effect of risk factors related to the characteristics and clinical history of the population, laboratory test results, drug management, and type of ventilation on the probability of survival/discharge from the ICU. A retrospective cohort multicentric study of adults with COVID-19 admitted to the ICU between March 2020 and December 2021. Data were collected from 6 hospitals in 5 cities in Ecuador. The primary outcome was ICU survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Of those admitted to the ICU with COVID-19, (n = 991), mean age was 56.76 ±â€…13.14, and 65.9% were male. Regarding the primary outcome, 51.1% (n = 506) died and 48.9% (n = 485) survived. Of the group that died, their mean age was higher than the survivors (60.7 vs 52.60 years, respectively), and they had a higher prevalence of comorbidities such as arterial hypertension (37.2% vs 20.4%, respectively) and diabetes mellitus (26.9% vs 15.7%, respectively), with P < .001. In ventilatory management, 32.7% of patients used noninvasive ventilation and high-flow nasal cannula, and 67.3% required invasive ventilatory support. After adjusting for confounders, Cox regression analysis showed that patients were less likely to be discharged alive from the ICU if they met the following conditions: arterial hypertension (hazard ratio [HR] = 0.83 95% CI 0.723-0.964), diabetes mellitus (HR = 0.80 95% CI 0.696-0.938), older than 62 years (HR = 0.86 95% CI 0.790-0.956), obese (body mass index ≥ 30) (HR = 0.78 95% CI 0.697-0.887), 1 unit increase in SOFA score (HR = 0.94 95% CI 0.937-0.961), PaO2/FiO2 ratio <100 mm Hg (HR = 0.84 95% CI 0.786-0.914), and the use of invasive mechanical ventilation (HR = 0.68 95% CI 0.614-0.769). Risk factors associated with increased mortality were older age, obesity, arterial hypertension, and diabetes. Factors such as male gender, chronic obstructive pulmonary disease, acute kidney injury, and cancer reported in other investigations did not have the same effect on mortality in our study.


Asunto(s)
COVID-19 , Unidades de Cuidados Intensivos , Humanos , Masculino , COVID-19/mortalidad , COVID-19/epidemiología , Persona de Mediana Edad , Femenino , Ecuador/epidemiología , Estudios Retrospectivos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Factores de Riesgo , Anciano , Adulto , Comorbilidad , Mortalidad Hospitalaria , SARS-CoV-2 , Respiración Artificial/estadística & datos numéricos , Modelos de Riesgos Proporcionales
17.
Genetics ; 227(4)2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-38963803

RESUMEN

Radiotherapy is a key treatment option for a wide variety of human tumors, employed either alone or alongside with other therapeutic interventions. Radiotherapy uses high-energy particles to destroy tumor cells, blocking their ability to divide and proliferate. The effectiveness of radiotherapy is due to genetic and epigenetic factors that determine how tumor cells respond to ionizing radiation. These factors contribute to the establishment of resistance to radiotherapy, which increases the risk of poor clinical prognosis of patients. Although the mechanisms by which tumor cells induce radioresistance are unclear, evidence points out several contributing factors including the overexpression of DNA repair systems, increased levels of reactive oxygen species, alterations in the tumor microenvironment, and enrichment of cancer stem cell populations. In this context, dysregulation of microRNAs or miRNAs, critical regulators of gene expression, may influence how tumors respond to radiation. There is increasing evidence that miRNAs may act as sensitizers or enhancers of radioresistance, regulating key processes such as the DNA damage response and the cell death signaling pathway. Furthermore, expression and activity of miRNAs have shown informative value in overcoming radiotherapy and long-term radiotoxicity, revealing their potential as biomarkers. In this review, we will discuss the molecular mechanisms associated with the response to radiotherapy and highlight the central role of miRNAs in regulating the molecular mechanisms responsible for cellular radioresistance. We will also review radio-miRs, radiotherapy-related miRNAs, either as sensitizers or enhancers of radioresistance that hold promise as biomarkers or pharmacological targets to sensitize radioresistant cells.


Asunto(s)
MicroARNs , Neoplasias , Tolerancia a Radiación , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Tolerancia a Radiación/genética , Neoplasias/radioterapia , Neoplasias/genética , Neoplasias/metabolismo , Reparación del ADN , Animales , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Daño del ADN
18.
Antioxidants (Basel) ; 13(6)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38929103

RESUMEN

Microbial community control is crucial for maintaining homeostasis of the gut-liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)-Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)-enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice's liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.

19.
Methods Mol Biol ; 2825: 213-237, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38913312

RESUMEN

Three-dimensional structured illumination microscopy (3D-SIM) and fluorescence in situ hybridization on three-dimensional preserved cells (3D-FISH) have proven to be robust and efficient methodologies for analyzing nuclear architecture and profiling the genome's topological features. These methods have allowed the simultaneous visualization and evaluation of several target structures at super-resolution. In this chapter, we focus on the application of 3D-SIM for the visualization of 3D-FISH preparations of chromosomes in interphase, known as Chromosome Territories (CTs). We provide a workflow and detailed guidelines for sample preparation, image acquisition, and image analysis to obtain quantitative measurements for profiling chromosome topological features. In parallel, we address a practical example of these protocols in the profiling of CTs 9 and 22 involved in the translocation t(9;22) in Chronic Myeloid Leukemia (CML). The profiling of chromosome topological features described in this chapter allowed us to characterize a large-scale topological disruption of CTs 9 and 22 that correlates directly with patients' response to treatment and as a possible potential change in the inheritance systems. These findings open new insights into how the genome structure is associated with the response to cancer treatments, highlighting the importance of microscopy in analyzing the topological features of the genome.


Asunto(s)
Imagenología Tridimensional , Hibridación Fluorescente in Situ , Humanos , Hibridación Fluorescente in Situ/métodos , Imagenología Tridimensional/métodos , Translocación Genética , Cromosomas/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Interfase/genética , Cromosomas Humanos/genética , Procesamiento de Imagen Asistido por Computador/métodos
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